Marginal Zone B Cell Responses To Antigens

Antibody (Ab) responses are classified as T-dependent (TD) and T-independent responses according to whether B cells receive T cell help. However, these two types of responses rely on different B cell subsets: follicular (FO) versus marginal zone (MZ) B cells, and occur in particular locations, B cell follicles versus spleen MZ. In contrast to FO B cells engaged in the TD response against protein antigens (Ags), MZ B cells preferentially recognize nonprotein Ags, rapidly produce poly/self-reactive IgM (or IgG) of low affinity for invading pathogens and eventually form nonproductive germinal centers but rarely generate long-lived plasma cells or memory B cells. Recent data show that MZ B cells receive key helper signals from neutrophils and type 3 innate-like cells within the MZ for mounting protective Ab responses. Being CD1(hi), MZ B cells can also present glycolipids to invariant natural killer T cell (iNKT) and establish cognate interactions leading to the production of glycolipid-specific Abs and iNKT activation. Through their continuous shuttling between MZ and follicles, MZ B cells can rapidly instruct FO B cells of any Ag change in MZ-associated blood flow. Here we highlight the phenotypic and functional particularities of MZ B cells in rodents and humans, and show how MZ B cells co-opt a diversity of innate helper cells, cleverly positioned in the MZ, to boost their Ab responses.